1. Field of the Invention
This invention pertains to a method for treating ulcerative colitis. Specifically, the method comprises orally or rectally administering to a human having ulcerative colitis a therapeutically effective amount of an antibody which binds to a tropomyosin isoform associated with ulcerative colitis. In another embodiment, the invention pertains to a method for treating ulcerative colitis in a human which comprises the steps of (a) obtaining from a human a colon epithelial cell extract containing a tropomyosin isoform associated with ulcerative colitis; (b) purifying the tropomyosin isoform until the tropomyosin isoform is substantially homogeneous; (c) developing an antibody which binds to the tropomyosin isoform; and (d) orally or rectally administering to a human having ulcerative colitis a therapeutically effective amount of the antibody to bind to the tropomyosin isoform associated with ulcerative colitis. In yet another embodiment, the invention pertains to a method for treating ulcerative colitis in a human which comprises orally administering to the human a therapeutically effective amount of a tropomyosin isoform associated with ulcerative colitis.
2. Description of the Background
The disclosures referred to herein to illustrate the background of the invention and to provide additional detail with respect to its practice are incorporated herein by reference and, for convenience, are numerically referenced in the following text and respectively grouped in the appended bibliography.
Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) of unknown etiology, although autoimmunity has been emphasized in the pathogenesis of the disease (1). A marked increase in the mucosal IgG immunocytes (2) and IgG antibodies against colonic antigens (3) and neutrophil antigen (4) have been reported in ulcerative colitis colon. However, the specific antigen(s) involved in the IgG-immune recognition has not been clarified. The mucosal IgG overproduction could play pathogenetic role in ulcerative colitis as the subclass distribution of IgG-producing cells in both active and inactive ulcerative colitis lesions shows a disproportionate local overproduction of IgG1 (5,6). IgG1 antibodies are more effective in complement activation than IgG2 (7) and because of this property, IgG1 antibodies can contribute to the perpetuation of tissue damage in ulcerative colitis.
The presence of tissue-bound IgG antibody in the ulcerative colitis colon has been reported (8) and it was demonstrated that this IgG antibody recognized an Mr 40K colonic protein, (p40) (9). Tissue-bound IgG eluted from Crohn""s disease of the colon (CD) and controls did not recognize the p40, suggesting an autoantigenic role of this protein in ulcerative colitis (9). By immunocytochemical methods, other investigators reported the deposition of IgG1 autoantibody and activated complement products on the colonic epithelium from active ulcerative colitis (10,11), but not in Crohn""s colitis (12). Recently, p40 was purified from the colon to homogeneity, partially sequenced, and the two peptides derived therefrom showed 93-100% identity with the cytoskeletal protein tropomyosins (TMs) (13). Tropomyosins are cytoskeletal microtubular proteins present in all eukaryotic cells with organ specific isoforms, and multiple isoforms may be present in the same cell (14). At least 8 tropomyosin isoforms have been identified from human fibroblast cells (15) and strong evidence for the distinct functions performed by different tropomyosin isoforms has recently been generated (14). Tropomyosins are capable of inducing significant immune responses related to allergy (16) as well as autoimmunity (17). In a computer-based physico-chemical analysis, several sequences of tropomyosin-residues were considered to be among the most potent autoantigens (17). It has been reported that blood serum from patients with ulcerative colitis, but not from Crohn""s colitis and other controls, had IgG antibodies reactive to tropomyosins (13). The specific tropomyosin isoform(s) present in the human colon epithelium is unknown.